Panagiotaki Katerina N, Sideratou Zili, Vlahopoulos Spiros A, Paravatou-Petsotas Maria, Zachariadis Michael, Khoury Nikolas, Zoumpourlis Vassilis, Tsiourvas Dimitris
Institute of Nanoscience and Nanotechnology, NCSR ''Demokritos", 15310 Aghia Paraskevi, Greece.
Ηoremeio Research Laboratory, First Department of Paediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Pharmaceuticals (Basel). 2017 Nov 21;10(4):91. doi: 10.3390/ph10040091.
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication. The anticancer activity of this system against two aggressive DOX-resistant human prostate adenocarcinoma cell lines and in in vivo animal studies was assessed. The co-administration of encapsulated DOX and CQ leads to improved cell proliferation inhibition at extremely low DOX concentrations (0.25 μΜ). In vivo experiments against DU145 human prostate cancer cells grafted on immunodeficient mice resulted in tumor growth arrest during the three-week administration period and no pervasive side effects. The findings put forward the potential of such targeted low dose combination treatments as a therapeutic scheme with minimal adverse effects.
靶向亚细胞器尤其是线粒体的药物递送系统，被认为在治疗与线粒体功能障碍相关的疾病（包括癌症或神经退行性疾病）方面具有巨大潜力。为此，开发了一种新型的超支化线粒体靶向纳米载体，用于高效共递送两种不同（在化学和药理学方面均不同）的生物活性化合物。该载体基于用三苯基膦基团功能化的超支化聚（乙烯亚胺），在水性介质中形成直径约100nm的纳米颗粒，并且可以包封阿霉素（DOX），一种著名的抗癌药物，以及氯喹（CQ），一种在抗癌药物中具有潜在应用前景的已知化学增敏剂。评估了该系统对两种侵袭性阿霉素耐药的人前列腺腺癌细胞系的抗癌活性以及在体内动物研究中的活性。在极低的阿霉素浓度（0.25μM）下，共施用包封的阿霉素和氯喹可导致细胞增殖抑制得到改善。针对移植到免疫缺陷小鼠上的DU145人前列腺癌细胞进行的体内实验，在为期三周的给药期内导致肿瘤生长停滞，并且没有普遍的副作用。这些发现提出了这种靶向低剂量联合治疗作为一种具有最小副作用的治疗方案的潜力。
